Is CDC45 p.Arg341Trp (c.1021C>T) pathogenic?

CDC45 p.Arg341Trp (c.1021C>T) is classified Conflicting classifications of pathogenicity in CDC45 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-04-20). AlphaMissense: likely benign (0.1055); Very rare (popmax 0.00851%, nfe); Associated with Meier-Gorlin syndrome 7.

What condition is associated with CDC45 p.Arg341Trp (c.1021C>T)?

CDC45 p.Arg341Trp (c.1021C>T) is associated with Meier-Gorlin syndrome 7 (ClinVar).

How common is CDC45 p.Arg341Trp (c.1021C>T) in the general population?

CDC45 p.Arg341Trp (c.1021C>T) is very rare (popmax 0.00851%, nfe) (gnomAD).

What do computational predictors say about CDC45 p.Arg341Trp (c.1021C>T)?

AlphaMissense predicts likely benign (score 0.1055) — an in-silico prediction, not a clinical call.

CDC45 p.Arg341Trp

c.1021C>T · rs540900837 · VCV635406

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1055 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00851%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Meier-Gorlin syndrome 7

Computational evidence

Protein change
AlphaMissense	0.1055	likely benign
REVEL	0.285	benign-leaning
SaProt	LLR -6.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.86, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 39 kb · p 0.0069 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00851% European (non-Finnish) · 100/1,175,482 alleles

Filtering AF 0.0071% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00662%

Overall 0.00675% 108/1,599,206 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00851%	11,755
East Asian	0.00447%	22,390
South Asian	0.00344%	29,095
Remaining individualsnot grpmax-eligible	0.00322%	31,015
African / African-American	0.00135%	74,030

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CDC45
Protein: p.Arg341Trp
Coding: c.1021C>T
MANE Select: NM_003504
dbSNP: rs540900837
Type: single nucleotide variant
Location: chr22:19507830 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.59 · 7 PDB
Residue 341: an α-helix

Full CDC45 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Meier-Gorlin syndrome 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDC45 p.Arg341Gln Uncertain significance ★ ⚠ same residue
CDC45 p.Pro463Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
CDC45 p.Ile509Val Uncertain significance ★★ ⚠ same condition
CDC45 p.Pro496Leu Uncertain significance ★★ ⚠ same condition
CDC45 p.Ala298Val Likely pathogenic ★ ⚠ same condition
CDC45 p.Asn76His Likely pathogenic ★ same condition
CDC45 p.Asp226Gly Likely pathogenic ★ ⚠ same condition
CDC45 p.Gln68Arg Likely pathogenic ★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cdc45-p-arg341trp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown